Studies on a "melanoma specific" antigen of 250K daltons and a 100K "common" tumor antigen have led to a further understanding of the biology of human melanoma. The 100K antigen was identified in normal human serum and shown to cross-react with C-reactive protein, an acute phase reactant. In addition, serum antigen was shown to circulate as an immune complex with IgG and IgM. Further, the serum form of 100K was found to be evolutionarily restricted to higher apes and man. The 250K antigen was found to be present on other tumors of neural-crest origin, particularly glioblastomas but to differ in molecular form and biosynthesis. As a target for serotherapy with monoclonal antibody, the 250K antigen was found to be ideal because analysis of clones of primary human melanoma cells indicated a lack of qualitative heterogeneity in antigen-expression. Finally, conditions for establishing nude mouse-human lymphoid chimeras have been delineated, enabling us to test the feasibility of this project.